1. Field of the Invention
This invention relates to novel compounds and methods which are useful for inhibiting the replication of DNA viruses, and more particularly, relates to compounds for inhibiting the replication of DNA viruses which induce the formation of thymidine kinase enzyme.
2. History of the Prior Art
Historically, viruses have been the causative agents of many diseases of both plants and animals including man. Diseases caused by viruses have been very difficult to control or cure by traditional methods. Many such viral diseases have been, in the past, effectively controlled through mass vaccination but even in modern times, effective agents to cure viral diseases, rather than prevent them, have been unavailable.
It has been recently discovered that certain substituted naturally occurring pyrimidinones are effective antiviral agents. Most of such compounds are 5-substituted pyrimidinones attached to a pentose sugar group at the one position of the pyrimidinone ring. Examples of such compounds and their effects are discussed in "Molecular Basis for Serendipitous Development of Antiviral and Anticancer Aminonucleosides" by W. H. Prusoff et al; "Comparative Study of the Potency and Selectivity of Anti-Herpes Compounds" by DeClercq and "Strategy for the Development of Selective Anti-Herpes Virus Agents Based on the Unique Properties of Viral Induced Enzymes--Thymidine Kinase, DNase and DNA Polymerase". All of these articles appear in Volume 57 of a Symposium of the Federation of European Biochemical Societies, Antimetabolites in Biochemistry, Biology and Medicine edited by Skoda et al, published by Pergamon Press (1978).
Unfortunately, such antiviral compounds, based upon naturally occurring pyrimidinones have a serious disadvantage in that these compounds are rapidly metabolized, generally having a metabolic half life of less than 30 minutes. Such short metabolic life has not permitted such compounds to be effectively used under In Vivo conditions.
Certain compounds, based upon 4-Deoxo uracil have recently been synthesized by two of the inventors herein and presented in a thesis by Alan Curtis Schroeder in 1978. Such thesis does not in general discuss or suggest any anti-viral activity by 5 substituted 4-Deoxo uracil compounds except on page 98 of the thesis wherein it was indicated that such compounds would be tested against Herpes Virus in mouse L cells. There was no indication that such compounds would in fact have any effect after such tests.